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Chronic Liver Disease: Latest Research in Pathogenesis, Detection and Treatment

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (15 March 2023) | Viewed by 40384

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Dr. Cristian Turato

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Guest Editor

Department of Molecular Medicine, University of Pavia, 27100 Pavia, Italy
Interests: liver cancer; liver fibrosis; NASH; liver signalling; liver models of disease; oxidative stress
Special Issues, Collections and Topics in MDPI journals

Dr. Stefania Cannito

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Department of Clinical and Biological Sciences, University of Torino, 10125 Torino, Italy
Interests: liver disease; cancer research; liver fibrosis; metabolism and liver; oxidative stress
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Chronic liver diseases (CLDs) are a major challenge for global health. In patients with CLDs, liver cirrhosis and hepatocellular carcinoma (HCC) are the main contributors to morbidity and mortality, and remain a significant clinical problem. Chronic liver injuries are characterized by: 1) reiteration of liver injury and persisting inflammation as a major driving force for progressive fibrogenesis, resulting in increased deposition of extracellular matrix or ECM, eventually leading to cirrhosis and liver failure; 2) cellular levels that predominate the involvement of macrophages and Kupffer cells as well as highly proliferative, profibrogenic, migrating and contractile myofibroblast (MF)-like cells that may originate, following activation, from hepatic stellate cells (HSC/MFs). Several mechanisms can sustain fibrogenesis and its progression to advanced liver fibrosis, cirrhosis, liver failure and the development of HCC. Because of high incidence and mortality, there is a need to better understanding the mechanisms underlying the transition process from a healthy liver to end-stage disease in order to predict patients at a high risk of developing HCC, to detect HCC at an early stage and to predict evolution, recurrence and outcome after treatment.

In this Special Issue, I invite you to contribute original and cutting-edge research articles and reviews related to the title Chronic Liver Disease: Latest Research in Pathogenesis, Detection and Treatment.

Dr. Cristian Turato
Dr. Stefania Cannito
Guest Editors

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Keywords

NASH/NAFLD: pathogenesis, detection, and treatment
hepatocellular carcinoma: pathogenesis, detection, and treatment
inflammation in liver disease
3D liver models
microbiota and liver disease
mechanisms of damage and repair: ischemia-riperfusion injury
cellular pathology in acute and chronic liver damage of different origin
biomarkers in liver disease: emerging methods and potential applications
immunology in the liver—from homeostasis to disease

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Published Papers (13 papers)

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Editorial

Jump to: Research, Review

4 pages, 192 KiB

Open AccessEditorial

Chronic Liver Disease: Latest Research in Pathogenesis, Detection and Treatment

by Silvia De Siervi, Stefania Cannito and Cristian Turato

Int. J. Mol. Sci. 2023, 24(13), 10633; https://doi.org/10.3390/ijms241310633 - 25 Jun 2023

Cited by 5 | Viewed by 2464

Abstract

Chronic liver disease (CLD) is a major global health threat and has emerged as a leading cause of human death [...] Full article

(This article belongs to the Special Issue Chronic Liver Disease: Latest Research in Pathogenesis, Detection and Treatment)

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17 pages, 3021 KiB

Open AccessArticle

Detection of Novel Biomarkers in Pediatric Autoimmune Hepatitis by Proteomic Profiling

by Claudia Sîrbe, Medeea Badii, Tania O. Crişan, Gabriel Bența, Alina Grama, Leo A. B. Joosten, Simona Rednic and Tudor Lucian Pop

Int. J. Mol. Sci. 2023, 24(8), 7479; https://doi.org/10.3390/ijms24087479 - 19 Apr 2023

Cited by 3 | Viewed by 2610

Abstract

Autoimmune hepatitis (AIH) is characterized by immune-mediated hepatocyte injury resulting in the destruction of liver cells, causing inflammation, liver failure, and fibrosis. Pediatric (AIH) is an autoimmune inflammatory disease that usually requires immunosuppression for an extended period. Frequent relapses after treatment discontinuation demonstrate that current therapies do not control intrahepatic immune processes. This study describes targeted proteomic profiling data in patients with AIH and controls. A total of 92 inflammatory and 92 cardiometabolic plasma markers were assessed for (i) pediatric AIH versus controls, (ii) AIH type 1 versus type 2, (iii) AIH and AIH–autoimmune sclerosing cholangitis overlapping syndrome and (iv) correlations with circulating vitamin D levels in AIH. A total of 16 proteins showed a nominally significant differential abundance in pediatric patients with AIH compared to controls. No clustering of AIH subphenotypes based on all protein data was observed, and no significant correlation of vitamin D levels was observed for the identified proteins. The proteins that showed variable expression include CA1, CA3, GAS6, FCGR2A, 4E-BP1 and CCL19, which may serve as potential biomarkers for patients with AIH. CX3CL1, CXCL10, CCL23, CSF1 and CCL19 showed homology to one another and may be coexpressed in AIH. CXCL10 seems to be the central intermediary link for the listed proteins. These proteins were involved in relevant mechanistic pathways for liver diseases and immune processes in AIH pathogenesis. This is the first report on the proteomic profile of pediatric AIH. The identified markers could potentially lead to new diagnostic and therapeutic tools. Nevertheless, considering the complex pathogenesis of AIH, more extensive studies are warranted to replicate and validate the present study’s findings. Full article

(This article belongs to the Special Issue Chronic Liver Disease: Latest Research in Pathogenesis, Detection and Treatment)

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21 pages, 1437 KiB

Open AccessArticle

Diagnostic Significance of hsa-miR-21-5p, hsa-miR-192-5p, hsa-miR-155-5p, hsa-miR-199a-5p Panel and Ratios in Hepatocellular Carcinoma on Top of Liver Cirrhosis in HCV-Infected Patients

by Mona A. Eldosoky, Reham Hammad, Asmaa A. Elmadbouly, Reda Badr Aglan, Sherihan G. AbdelHamid, Mohamed Alboraie, Donia Ahmed Hassan, Mohamed A. Shaheen, Areej Rushdi, Reem M. Ahmed, Alzahra Abdelbadea, Neamat A. Abdelmageed, Ahmed Elshafei, Elham Ali, Omaima I. Abo-Elkheir, Samy Zaky, Nadia M. Hamdy and Claude Lambert

Int. J. Mol. Sci. 2023, 24(4), 3157; https://doi.org/10.3390/ijms24043157 - 5 Feb 2023

Cited by 23 | Viewed by 3794

Abstract

Early hepatocellular carcinoma (HCC) diagnosis is challenging. Moreover, for patients with alpha-fetoprotein (AFP)-negative HCC, this challenge is augmented. MicroRNAs (miRs) profiles may serve as potential HCC molecular markers. We aimed to assess plasma homo sapiens—(hsa)-miR-21-5p, hsa-miR-155-5p, hsa-miR-192-5p, and hsa-miR-199a-5p—expression levels as a panel of biomarkers for HCC in chronic hepatitis C virus (CHCV) patients with liver cirrhosis (LC), especially AFP-negative HCC cases, as a step toward non-protein coding (nc) RNA precision medicine. Subjects and methods: 79 patients enrolled with CHCV infection with LC, subclassified into an LC group without HCC (n = 40) and LC with HCC (n = 39). Real-time quantitative PCR was used to measure plasma hsa-miR-21-5p, hsa-miR-155-5p, hsa-miR-192-5p, and hsa-miR-199a-5p. Results: Plasma hsa-miR-21-5p and hsa-miR-155-5p demonstrated significant upregulation, while hsa-miR-199a-5p demonstrated significant downregulation in the HCC group (n = 39) when compared to the LC group (n = 40). hsa-miR-21-5p expression was positively correlated with serum AFP, insulin, and insulin resistance (r = 0.5, p < 0.001, r = 0.334, p = 0.01, and r = 0.303, p = 0.02, respectively). According to the ROC curves, for differentiating HCC from LC, combining AFP with each of hsa-miR-21-5p, hsa-miR-155-5p, and miR199a-5p improved the diagnostic sensitivity to 87%, 82%, and 84%, respectively, vs. 69% for AFP alone, with acceptable specificities of 77.5%, 77.5%, and 80%, respectively, and AUC = 0.89, 0.85, and 0.90, respectively vs. 0.85 for AFP alone. hsa-miR-21-5p/hsa-miR-199a-5p and hsa-miR-155-5p/hsa-miR-199a-5p ratios discriminated HCC from LC at AUC = 0.76 and 0.71, respectively, with sensitivities = 94% and 92% and specificities = 48% and 53%, respectively. Upregulation of plasma hsa-miR-21-5p was considered as an independent risk factor for HCC development [OR = 1.198(1.063–1.329), p = 0.002]. Conclusions: Combining each of hsa-miR-21-5p, hsa-miR-155-5p, and hsa-miR-199a-5p with AFP made it possible to identify HCC development in the LC patients’ cohort with higher sensitivity than using AFP alone. hsa-miR-21-5p/hsa-miR-199a-5p and hsa-miR-155-5p/hsa-miR-199a-5p ratios are potential HCC molecular markers for AFP-negative HCC patients. hsa-miR-21-5p was linked, clinically and via in silico proof, to insulin metabolism, inflammation, dyslipidemia, and tumorigenesis in the HCC patients’ group as well as for an upregulated independent risk factor for the emergence of HCC from LC in the CHCV patients. Full article

(This article belongs to the Special Issue Chronic Liver Disease: Latest Research in Pathogenesis, Detection and Treatment)

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20 pages, 44100 KiB

Open AccessArticle

Lipid Droplet-Associated Proteins Perilipin 1 and 2: Molecular Markers of Steatosis and Microvesicular Steatotic Foci in Chronic Hepatitis C

by Selina Schelbert, Mario Schindeldecker, Uta Drebber, Hagen Roland Witzel, Arndt Weinmann, Volker Dries, Peter Schirmacher, Wilfried Roth and Beate Katharina Straub

Int. J. Mol. Sci. 2022, 23(24), 15456; https://doi.org/10.3390/ijms232415456 - 7 Dec 2022

Cited by 6 | Viewed by 2786

Abstract

Chronic infection with hepatitis C (HCV) is a major risk factor in the development of cirrhosis and hepatocellular carcinoma. Lipid metabolism plays a major role in the replication and deposition of HCV at lipid droplets (LDs). We have demonstrated the importance of LD-associated proteins of the perilipin family in steatotic liver diseases. Using a large collection of 231 human liver biopsies with HCV, perilipins 1 and 2 have been localized to LDs of hepatocytes that correlate with the degree of steatosis and specific HCV genotypes, but not significantly with the HCV viral load. Perilipin 1- and 2-positive microvesicular steatotic foci were observed in 36% of HCV liver biopsies, and also in chronic hepatitis B, autoimmune hepatitis and mildly steatotic or normal livers, but less or none were observed in normal livers of younger patients. Microvesicular steatotic foci did not frequently overlap with glycogenotic/clear cell foci as determined by PAS stain in serial sections. Steatotic foci were detected in all liver zones with slight architectural disarrays, as demonstrated by immunohistochemical glutamine synthetase staining of zone three, but without elevated Ki67-proliferation rates. In conclusion, microvesicular steatotic foci are frequently found in chronic viral hepatitis, but the clinical significance of these foci is so far not clear. Full article

(This article belongs to the Special Issue Chronic Liver Disease: Latest Research in Pathogenesis, Detection and Treatment)

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14 pages, 2454 KiB

Open AccessArticle

Hepatic Sam68 Regulates Systemic Glucose Homeostasis and Insulin Sensitivity

by Aijun Qiao, Wenxia Ma, Ying Jiang, Chaoshan Han, Baolong Yan, Junlan Zhou and Gangjian Qin

Int. J. Mol. Sci. 2022, 23(19), 11469; https://doi.org/10.3390/ijms231911469 - 29 Sep 2022

Cited by 2 | Viewed by 2665

Abstract

Hepatic glucose production (HGP) is an important component of glucose homeostasis, and deregulated HGP, particularly through gluconeogenesis, contributes to hyperglycemia and pathology of type-2 diabetes (T2D). It has been shown that the gluconeogenic gene expression is governed primarily by the transcription factor cAMP-response element (CRE)-binding protein (CREB) and its coactivator, CREB-regulated transcriptional coactivator 2 (CRTC2). Recently, we have discovered that Sam68, an adaptor protein and Src kinase substrate, potently promotes hepatic gluconeogenesis by promoting CRTC2 stability; however, the detailed mechanisms remain unclear. Here we show that in response to glucagon, Sam68 increases CREB/CRTC2 transactivity by interacting with CRTC2 in the CREB/CRTC2 complex and occupying the CRE motif of promoters, leading to gluconeogenic gene expression and glucose production. In hepatocytes, glucagon promotes Sam68 nuclear import, whereas insulin elicits its nuclear export. Furthermore, ablation of Sam68 in hepatocytes protects mice from high-fat diet (HFD)-induced hyperglycemia and significantly increased hepatic and peripheral insulin sensitivities. Thus, hepatic Sam68 potentiates CREB/CRTC2-mediated glucose production, contributes to the pathogenesis of insulin resistance, and may serve as a therapeutic target for T2D. Full article

(This article belongs to the Special Issue Chronic Liver Disease: Latest Research in Pathogenesis, Detection and Treatment)

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14 pages, 8199 KiB

Open AccessArticle

IL-17A in Human Liver: Significant Source of Inflammation and Trigger of Liver Fibrosis Initiation

by Daria Kartasheva-Ebertz, Jesintha Gaston, Loriane Lair-Mehiri, Estelle Mottez, Tan-Phuc Buivan, Pierre-Philippe Massault, Olivier Scatton, Sebastien Gaujoux, Jean-Christophe Vaillant, Stanislas Pol and Sylvie Lagaye

Int. J. Mol. Sci. 2022, 23(17), 9773; https://doi.org/10.3390/ijms23179773 - 29 Aug 2022

Cited by 11 | Viewed by 2148

Abstract

IL-17A is considered to guide liver inflammation and fibrosis. From twenty-two human liver samples of different fibrosis stages (F0 to F4), IL-17A, IL-22, and TGFβ1 protein expression in liver tissue lysates were analyzed. Ten paired samples of liver tissue (F0–F1 stage) and blood from the same patient were used to analyze intrahepatic and blood T-lymphoid IL-17A⁺ cells by flow cytometry. The analyses have been performed regardless of pathology, considering the stage of fibrosis. Human liver tissue was used for the primary human liver slice cultures, followed by subsequent cytokine stimulation and fibrotic markers’ analysis by ELISA. IL-17A production in human liver tissue was significantly higher in the early fibrotic stage compared with the advanced stage. Th17 T cells and, to a lesser extent, MAIT cells were the main sources of IL-17A in both compartments, the liver and the blood. Moreover, the presence of liver Th17IL-17A⁺INFγ⁺ cells was detected in the liver. IL-17A stimulation of human liver slice culture increased the expression of profibrotic and pro-inflammatory markers. IL-17A, secreted by Th17 and MAIT cells in the liver, triggered fibrosis by inducing the expression of IL-6 and profibrotic markers and could be a target for antifibrotic treatment. Further amplitude studies are needed to confirm the current results. Full article

(This article belongs to the Special Issue Chronic Liver Disease: Latest Research in Pathogenesis, Detection and Treatment)

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15 pages, 3813 KiB

Open AccessArticle

Transcriptomic Analyses Reveal Long Non-Coding RNA in Peripheral Blood Mononuclear Cells as a Novel Biomarker for Diagnosis and Prognosis of Hepatocellular Carcinoma

by Pattapon Kunadirek, Nutcha Pinjaroen, Intawat Nookaew, Pisit Tangkijvanich and Natthaya Chuaypen

Int. J. Mol. Sci. 2022, 23(14), 7882; https://doi.org/10.3390/ijms23147882 - 17 Jul 2022

Cited by 11 | Viewed by 2542

Abstract

Novel biomarkers are highly required for the diagnosis and predicting prognosis of hepatocellular carcinoma (HCC). In this study, we investigated the profiles of long non-coding RNAs (lncRNAs) obtained from the peripheral blood mononuclear cells (PBMCs) of patients with HCC and PBMCs from a co-culture model using transcriptomic analysis. The differentially expressed lncRNAs (DElncRNAs) were then characterized and integrated as cancer-induced lncRNAs. Among them, three up-regulating DElncRNAs including MIR4435-2HG, SNHG9 and lnc-LCP2-1 and one down-regulating, lnc-POLD3-2, were identified. The functional analysis showed that these enriched lncRNAs were mainly associated with carcinogenesis and immune responses. Following further validation in PBMCs samples (100 HBV-related HCC, 100 chronic hepatitis B and 100 healthy controls), MIR4435-2HG, lnc-POLD3-2 and their combination were revealed to be sensitive biomarkers in discriminating HCC from non-HCC (AUROC = 0.78, 0.80, and 0.87, respectively), particularly among individuals with normal serum alpha-fetoprotein levels. Additionally, high circulating SNHG9 expression was shown to be an independent prognostic factor of overall survival in patients with HCC. These results indicate that determining these lncRNAs in PBMCs could serve as novel diagnostic and prognostic biomarkers for HBV-related HCC. Full article

(This article belongs to the Special Issue Chronic Liver Disease: Latest Research in Pathogenesis, Detection and Treatment)

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Review

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20 pages, 991 KiB

Open AccessReview

Molecular Mechanisms Underlying Vascular Liver Diseases: Focus on Thrombosis

by Lucia Giuli, Maria Pallozzi, Giulia Venturini, Antonio Gasbarrini, Francesca Romana Ponziani and Francesco Santopaolo

Int. J. Mol. Sci. 2023, 24(16), 12754; https://doi.org/10.3390/ijms241612754 - 13 Aug 2023

Cited by 1 | Viewed by 2161

Abstract

Vascular liver disorders (VLDs) comprise a wide spectrum of clinical-pathological entities that primarily affect the hepatic vascular system of both cirrhotic and non-cirrhotic patients. VLDs more frequently involve the portal and the hepatic veins, as well as liver sinusoids, resulting in an imbalance of liver homeostasis with serious consequences, such as the development of portal hypertension and liver fibrosis. Surprisingly, many VLDs are characterized by a prothrombotic phenotype. The molecular mechanisms that cause thrombosis in VLD are only partially explained by the alteration in the Virchow’s triad (hypercoagulability, blood stasis, and endothelial damage) and nowadays their pathogenesis is incompletely described and understood. Studies about this topic have been hampered by the low incidence of VLDs in the general population and by the absence of suitable animal models. Recently, the role of coagulation imbalance in liver disease has been postulated as one of the main mechanisms linked to fibrogenesis, so a novel interest in vascular alterations of the liver has been renewed. This review provides a detailed analysis of the current knowledge of molecular mechanisms of VLD. We also focus on the promising role of anticoagulation as a strategy to prevent liver complications and to improve the outcome of these patients. Full article

(This article belongs to the Special Issue Chronic Liver Disease: Latest Research in Pathogenesis, Detection and Treatment)

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20 pages, 7686 KiB

Open AccessReview

The Role of Fucoxanthin in Non-Alcoholic Fatty Liver Disease

by Jessica Winarto, Dae-Geun Song and Cheol-Ho Pan

Int. J. Mol. Sci. 2023, 24(9), 8203; https://doi.org/10.3390/ijms24098203 - 3 May 2023

Cited by 12 | Viewed by 3734

Abstract

Chronic liver disease (CLD) has emerged as a leading cause of human deaths. It caused 1.32 million deaths in 2017, which affected men more than women by a two-to-one ratio. There are various causes of CLD, including obesity, excessive alcohol consumption, and viral infection. Among them, non-alcoholic fatty liver disease (NAFLD), one of obesity-induced liver diseases, is the major cause, representing the cause of more than 50% of cases. Fucoxanthin, a carotenoid mainly found in brown seaweed, exhibits various biological activities against NAFLD. Its role in NAFLD appears in several mechanisms, such as inducing thermogenesis in mitochondrial homeostasis, altering lipid metabolism, and promoting anti-inflammatory and anti-oxidant activities. The corresponding altered signaling pathways are the β3-adorenarine receptor (β3Ad), proliferator-activated receptor gamma coactivator (PGC-1), adenosine monophosphate-activated protein kinase (AMPK), peroxisome proliferator-activated receptor (PPAR), sterol regulatory element binding protein (SREBP), nuclear factor kappa B (NF-κB), mitogen-activated protein kinase (MAPK), protein kinase B (AKT), SMAD2/3, and P13K/Akt pathways. Fucoxanthin also exhibits anti-fibrogenic activity that prevents non-alcoholic steatohepatitis (NASH) development. Full article

(This article belongs to the Special Issue Chronic Liver Disease: Latest Research in Pathogenesis, Detection and Treatment)

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19 pages, 21483 KiB

Open AccessReview

Cocaine-Induced Time-Dependent Alterations in Cytochrome P450 and Liver Function

by Joanna Jastrzębska and Władysława Anna Daniel

Int. J. Mol. Sci. 2023, 24(2), 1632; https://doi.org/10.3390/ijms24021632 - 13 Jan 2023

Cited by 3 | Viewed by 3248

Abstract

Cytochrome P450 is responsible for the metabolism of endogenous substrates, drugs and substances of abuse. The brain and nervous system regulate liver cytochrome P450 via neuroendocrine mechanisms, as shown in rodents. Cocaine exerts its addictive effects through the dopaminergic system, the functioning of which undergoes changes during its continuous use. Therefore, it can be hypothesized that the regulation of cytochrome P450 by cocaine may also alter during the addiction process, cessation and relapse. We analyzed preclinical studies on the mechanisms of the pharmacological action of cocaine, the role of the brain’s dopaminergic system in the neuroendocrine regulation of cytochrome P450 and the in vitro and in vivo effects of cocaine on the cytochrome P450 expression/activity and hepatotoxicity. The results of passive cocaine administration indicate that cocaine affects liver cytochrome P450 enzymes (including those engaged in its own metabolism) via different mechanisms involving the expression of genes encoding cytochrome P450 enzymes and interaction with enzyme proteins. Thus, it may affect its own oxidative metabolism and the metabolism of endogenous substrates and other co-administered drugs and may lead to hepatotoxicity. Its effect depends on the specific cytochrome P450 enzyme affected, cocaine dosage, treatment duration and animal species. However, further complementary studies are needed to find out whether cocaine affects cytochrome P450 via the brain’s dopaminergic system. The knowledge of cocaine’s effect on cytochrome P450 function during the entire addiction process is still incomplete. There is a lack of information on the enzyme expression/activity in animals self-administering cocaine (addicted), in those withdrawn after cocaine self-administration, and during relapse in animals previously addicted; furthermore, there is no such information concerning humans. The subject of cytochrome P450 regulation by cocaine during the addiction process is an open issue, and addressing this topic may help in the treatment of drug abuse patients. Full article

(This article belongs to the Special Issue Chronic Liver Disease: Latest Research in Pathogenesis, Detection and Treatment)

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13 pages, 1234 KiB

Open AccessReview

Emerging Role of NLRP3 Inflammasome and Pyroptosis in Liver Transplantation

by Fernando Lucas-Ruiz, Alejandro Peñín-Franch, José Antonio Pons, Pablo Ramírez, Pablo Pelegrín, Santiago Cuevas and Alberto Baroja-Mazo

Int. J. Mol. Sci. 2022, 23(22), 14396; https://doi.org/10.3390/ijms232214396 - 19 Nov 2022

Cited by 14 | Viewed by 3356

Abstract

The nucleotide-binding domain leucine-rich repeat-receptor, pyrin domain-containing-3 (NLRP3) inflammasome contributes to the inflammatory response by activating caspase-1, which in turn participates in the maturation of interleukin (IL)-1β and IL-18, which are mainly secreted via pyroptosis. Pyroptosis is a lytic type of cell death that is controlled by caspase-1 processing gasdermin D. The amino-terminal fragment of gasdermin D inserts into the plasma membrane, creating stable pores and enabling the release of several proinflammatory factors. The activation of NLRP3 inflammasome and pyroptosis has been involved in the progression of liver fibrosis and its end-stage cirrhosis, which is among the main etiologies for liver transplantation (LT). Moreover, the NLRP3 inflammasome is involved in ischemia–reperfusion injury and early inflammation and rejection after LT. In this review, we summarize the recent literature addressing the role of the NLRP3 inflammasome and pyroptosis in all stages involved in LT and argue the potential targeting of this pathway as a future therapeutic strategy to improve LT outcomes. Likewise, we also discuss the impact of graft quality influenced by donation after circulatory death and the expected role of machine perfusion technology to modify the injury response related to inflammasome activation. Full article

(This article belongs to the Special Issue Chronic Liver Disease: Latest Research in Pathogenesis, Detection and Treatment)

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14 pages, 1780 KiB

Open AccessReview

Exosomal microRNAs and Progression of Nonalcoholic Steatohepatitis (NASH)

by Xiaoyan Qi and Jinping Lai

Int. J. Mol. Sci. 2022, 23(21), 13501; https://doi.org/10.3390/ijms232113501 - 4 Nov 2022

Cited by 7 | Viewed by 3535

Abstract

Nonalcoholic fatty liver disease (NAFLD)/metabolic associated fatty liver disease (MAFLD) is becoming a public health problem worldwide. Steatosis as the simple form and nonalcoholic steatohepatitis (NASH) as its progression form are commonly seen in liver biopsy specimens from patients with obesity, diabetes, hyperlipidemia, hypertension, and the use of certain drugs. Patients with NASH and advanced fibrosis were associated with increased risks of liver-related complications, including hepatocellular carcinoma (HCC). However, the mechanisms regarding the progression from simple steatosis to NASH fibrosis remain incompletely understood. Because NASH-caused liver injury is a complex process and multiple cell types are involved, intercellular communication is likely mediated by extracellular vesicles. Exosomes are a type of small extracellular vesicles and contain various cellular molecules, including proteins, messenger RNAs (mRNAs), and microRNAs (miRNAs). MiRNAs are short, non-coding RNA species that are important post-transcriptional regulators of gene expression and may play an important role in the pathogenesis of NALFD/NASH. In this article, we review the articles about NASH and exosomal miRNAs published in the most recent English literature through PubMed search and discuss the most recent criteria for histological diagnosis, pathogenesis from steatosis to NASH, roles of exosomal miRNAs in NASH pathogenesis and progression, as well as their potential in future clinical diagnosis and treatment for patients with NASH. Full article

(This article belongs to the Special Issue Chronic Liver Disease: Latest Research in Pathogenesis, Detection and Treatment)

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14 pages, 1835 KiB

Open AccessReview

Current Understanding in the Clinical Characteristics and Molecular Mechanisms in Different Subtypes of Biliary Atresia

by Lin He, Patrick Ho Yu Chung, Vincent Chi Hang Lui, Clara Sze Man Tang and Paul Kwong Hang Tam

Int. J. Mol. Sci. 2022, 23(9), 4841; https://doi.org/10.3390/ijms23094841 - 27 Apr 2022

Cited by 7 | Viewed by 3031

Abstract

Biliary atresia is a severe obliterative cholangiopathy in early infancy that is by far the most common cause of surgical jaundice and the most common indicator for liver transplantation in children. With the advanced knowledge gained from different clinical trials and the development of research models, a more precise clinical classification of BA (i.e., isolated BA (IBA), cystic BA (CBA), syndromic BA (SBA), and cytomegalovirus-associated BA (CMVBA)) is proposed. Different BA subtypes have similar yet distinguishable clinical manifestations. The clinical and etiological heterogeneity leads to dramatically different prognoses; hence, treatment needs to be specific. In this study, we reviewed the clinical characteristics of different BA subtypes and revealed the molecular mechanisms of their developmental contributors. We aimed to highlight the differences among these various subtypes of BA which ultimately contribute to the development of a specific management protocol for each subtype. Full article

(This article belongs to the Special Issue Chronic Liver Disease: Latest Research in Pathogenesis, Detection and Treatment)

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